It is known that the coenzyme Q10, a yellow crystalline powder having a melting point of about 50° C., is a liposoluble substance similar to a vitamin that is found inside the mitochondrial inner membrane, in which it performs a function as an integrating part for transporting electrons in oxidative phosphorylation. For this reason high mytochondrial levels of Coenzyme Q10 increase the cell energy level and protect from oxidative stress. CoQ10 is used as a food supplement, anti-oxidant and in the treatment of cardiovascular disorders, such as angina pectoris, hypertension and cardiac congestive failure. CoQ10 is practically insoluble in water and poorly absorbed by the gastro-intestinal tract due to its high molecular weight and poor hydrosolubility: it is therefore a challenge in the development of a formulation for oral administration.
Many approaches are known for formulating CoQ10 in orally administrable forms.
At present, as CoQ10 food supplements, capsules are available on the market that are oil-based or filled with powder, and also tablet form. However, the oral dissolution and bio-availability of such formulations vary greatly.
For example, known formulation strategies include: solubilized systems with soy lecithin, micellar solutions of CoQ10 with castor oil hydrogenated polyossimetilene (60), lipidic microspheres prepared as emulsified soy oil with phospholipids from egg yolk, re-dispersible dry emulsions, complexation of CoQ12 with cyclodextrin, drug self-emulsifier transport systems and solubilized forms of CQ10 in a mixture of polysorbate 80 and medium chain triglycerides.
For example, the following are known: the scientific articles “Emulsification of coenzyme Q10 using gum arabic increases bioavailability in rats and humans and improves food-processing suitability” in J. Nutr. Sci, Vitaminol., 56, 41-47, 2010 and “Improvement of the oral bioavailability of coenzyme Q10 by emulsification with fats and emulsifiers used in the food industry” LWT—Food Science and Technology 42 (2009) 385-390 and the patent applications EP-A-1782803, GB-A-2402334, US-A-2007/202166, US-A-2008/248013, US-A-2009/054530, US-A-2009/186009, WO-A-02/067864, WO-A-98/03170 and WO-A-2007/086689.
However, for most of these formulations the dissolution profiles are not reported, either due to their oily nature and poor hydrosolubility, or due to the absence of a suitable dissolution mean. Furthermore, these approaches entail long and costly procedures.
In particular, WO-A-2007/086689 (WO'689) describes a composition obtained using ethanol and dichloromethane solvents and subsequent spray drying. The composition in WO'689 is formed by five compounds, that is, hydroxypropyl methylcellulose (HPMC) as hydrophylic polymer, a sucrose-ester of fatty acids with HLB=12, CoQ10, DL-alpha-tocopheryl acetate (vitamin E) and silicon dioxide (silica or siloid). WO-A-2007/086689 mentions the use of maltodextrins as a hydrophylic polymer, but without providing specific examples of possible compositions with the maltodextrins, or experimental data thereon.
Consequently, there is a great need in the field to supply a composition based on ubidecarenone and to perfect a method to prepare it, which on the one hand improves the solubility and dissolution of the CoQ10 and on the other hand can be made efficiently, quickly and economically.
To solve the technical problems concerning the preparation of compositions in fine powder form comprising substantially active principles with poor solubility in a water or organic environment, for a long time now a process of dry co-grinding has been studied and perfected, in which an active principle is included in a hydrophylic or hydrophobic carrier, depending on the chemical-physical characteristics of the active principle in question, in the presence of an auxiliary co-grinding substance which allows a drastic reduction in the co-grinding times with undeniable advantages for the stability of the active principle.
This process, described in the international application WO-A-03/097012 (WO'012), allows to obtain ternary compositions—which include active principle/carrier/auxiliary co-grinding substance—whose properties of solubility and dissolution are considerably better than the corresponding binary compositions of active principle/carrier. Subsequently, it was also found that, by applying the processes described above to anti-oxidant agents, including ubidecarenone, to obtain compositions in fine powder form that is easily dispersed in a water environment and possibly soluble therein, the compositions obtained showed a considerable increase in the anti-oxidant power given the same content of active principle in solution, as described in the international application WO-A-2007/009997 (WO'997).
WO-A-2012/063217 discloses compositions for treating phonatory and olfactory apparatus disorders and containing coenzyme Q10, maltodextrins, sugar esters, dibasic calcium phosphate, vitamin A and colloidal silica.
JP-A-2005112744 discloses a ubidecarenone tablet prepared by tableting small granules produced from 12 to 30 w/w % of ubidecarenone, an inner granule vehicle (lactose, sucroses, D-mannitol, xylitol, or the like), and a binder (maltodextrin, water-soluble cellulose, or the like) by a wet granulation method, a disintegrator such as carmellose calcium or cross carmellose sodium and a lubricant, such as sucrose fatty acid ester or magnesium stearate.
It is therefore a purpose of the present invention to obtain a composition in fine powder form based on ubidecarenone and comprising at least a specific hydrophylic carrier and at least an adjuvant agent in particular ratios, which solves the shortcomings of the state of the art, in particular showing a further increase in solubility compared with the compositions obtained in the state of the art and a corresponding increased capacity of penetration into the mitochondrial membrane by the composition.
It is also a purpose of the present invention to obtain the composition for use in treatments in the cosmetic, pharmaceutical, dietary and food and veterinary fields
The Applicant has devised, tested and embodied the present invention to overcome the shortcomings of the state of the art and to obtain these and other purposes and advantages.
Unless otherwise defined, all the technical and scientific terms used here and hereafter have the same meaning as commonly understood by a person with ordinary experience in the field of the art to which the present invention belongs. Even if methods and materials similar or equivalent to those described here can be used in practice and in the trials of the present invention, the methods and materials are described hereafter as an example. In the event of conflict, the present application shall prevail, including its definitions. The materials, methods and examples have a purely illustrative purpose and shall not be understood restrictively.
The word “comprise” and variants of the word such as “comprises” and “comprising” are used here to indicate the inclusion of a clearly expressed whole or clearly expressed wholes but not the exclusion of any other whole or any other wholes, unless in the context or in use an exclusive interpretation of the word is required.
The word “consist” and variants of the word such as “consists” and “consisting” are used here to indicate the inclusion of a clearly expressed whole or clearly expressed wholes but not the exclusion of any other whole or any other wholes.